Studies on the roles for 8-nitroguanosine 3',5'-cyclic monophosphate in the cardiovascular system and the applications to drug discovery.

8-硝基鸟苷3,5-环单磷酸在心血管系统中的作用及其在药物发现中的应用研究。

• 批准号: 20590255
• 负责人: TOKUTOMI Yoshiko
• 金额: $ 3万
• 依托单位: Kumamoto University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2008
• 资助国家: 日本
• 起止时间: 2008 至 2010
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-20590255/
• 关键词: cGMP; eNOS; 心血管系; NO; 一酸化窒素; db; cGMP; eNOS; 心血管系; NO; 一酸化窒素; db

8-Nitroguanosine 3',5'-cyclic monophosphate (8-nitro-cGMP), formed nitric oxide (NO)-dependently, is a novel physiological second messenger. To study the physiological activity of 8-nitro-cGMP in the cardiovascular system, we studied its effects on vascular reactivity of mouse aortas. 8-Nitro-cGMP induced enhancement of contraction to phenylephrine and relaxation concentration-dependently in aortas from non-diabetic mice, but only relaxation in aortas from diabetic mice. It was suggested that 8-nitrocGMP- induced superoxide production via eNOS uncoupling may mediate the enhancement of the phenylephrine contraction. The vasodilator effect of 8-nitro-cGMP may contribute to amelioration of the vascular endothelial dysfunction in diabetic mice, representing a novel pharmacological approach toprevent the complications associated with diabetes.

8-硝基瓜烷氨酸3'，5'-循环单磷酸盐（8-硝基-CGMP）形成的一氧化氮（NO）依赖性地是一种新型的生理二信使。为了研究8-硝基-CGMP在心血管系统中的生理活性，我们研究了其对小鼠主动脉血管反应性的影响。 8-硝基-CGMP诱导了对苯肾上腺素的收缩增强，而在非糖尿病小鼠的主动脉中依赖于主动脉，但仅在糖尿病小鼠的主动脉中放松。有人提出，通过eNOS解偶联诱导8-亚硝化诱导的超氧化物的产生可能会介导苯肾上腺素收缩的增强。 8-硝基-CGMP的血管扩张效应可能有助于改善糖尿病小鼠血管内皮功能障碍，这代表了一种新型的药理方法，可以预防与糖尿病相关的并发症。